Air bubble removal from extracorporeal blood via chemical entrapment of nitrogen

ABSTRACT

A process includes removing air bubbles from extracorporeal blood via chemical entrapment of nitrogen (N2) gas.

BACKGROUND

Various medical treatments and procedures require a patient's blood tobe circulated outside the body (also referred to as an “extracorporealbloodstream”). Micro-leaks in bloodstream circulation equipment anddegassing effects from the blood may cause air bubbles to build up inthe extracorporeal bloodstream during medical treatments. Re-insertionof such air bubbles into the patient can lead to fatal embolisms. Toillustrate, cerebral microemboli generated during a cardiopulmonarybypass procedure may result in neurological impairment that is a majorcause of morbidity and mortality after open heart surgery.

There have been numerous attempts to remove microbubbles fromextracorporeal blood. While it is possible to remove larger air bubblesbefore the blood is re-inserted into the patient, there are challengesassociated with the removal of smaller air bubbles (also referred to as“microbubbles” having a diameter in a size range of about 2.5 μm to 50μm). Current solutions may enable partial mitigation of the air bubbleremoval problem (e.g., drip chambers) or may require undesired changesand interruptions in the treatments (e.g., reducing the bloodflow).Accordingly, there is a need for new techniques to efficiently andcontinuously remove microbubbles from extracorporeal bloodstreams inorder to reduce the risk of microemboli.

SUMMARY

According to an embodiment, a process comprises removing air bubblesfrom extracorporeal blood via chemical entrapment of nitrogen (N₂) gas.

According to another embodiment, an extracorporeal blood treatmentsystem is disclosed. The system includes an air bubble removal componentto remove air bubbles from extracorporeal blood via chemical entrapmentof nitrogen (N₂) gas.

According to another embodiment, an article of manufacture includes anorganometallic complex bound to a surface of a particle. Theorganometallic complex is utilized to remove air bubbles fromextracorporeal blood via chemical entrapment of nitrogen (N₂) gas bydinitrogen fixation.

The foregoing and other objects, features, and advantages of theinvention will be apparent from the following more particulardescriptions of exemplary embodiments of the invention as illustrated inthe accompanying drawings wherein like reference numbers generallyrepresent like parts of exemplary embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of an extracorporeal blood treatment system toremove air bubbles from extracorporeal blood via chemical entrapment ofnitrogen gas, according to one embodiment.

FIG. 2 is a diagram illustrating a particular embodiment of anextracorporeal blood treatment system that includes an air bubbleremoval component having multiple chambers of different surface-modifiedparticles, representing a multiple-stage approach to chemical entrapmentof nitrogen gas.

FIG. 3 is a flow diagram illustrating a particular embodiment of aprocess of removing air bubbles from extracorporeal blood via chemicalentrapment of nitrogen gas.

DETAILED DESCRIPTION

The present disclosure describes systems and methods of nitrogen gasremoval from extracorporeal blood via chemical entrapment. Nitrogen gas(N₂) represents the majority of the content (about 78 percent) of airbubbles that may be formed in extracorporeal blood as a result ofmicro-leaks in bloodstream circulation equipment and degassing effectsfrom the blood. In the present disclosure, the nitrogen gas in the airbubbles may be “fixed” via a reaction with a suitable organometalliccompound or a nitrogenase. As nitrogen gas represents the majority ofthe air bubble content, complexation of nitrogen may result in collapseof the air bubbles (including microbubbles). Accordingly, the systemsand methods of chemical entrapment of nitrogen gas described herein mayenable efficient and continuous removal of microbubbles from anextracorporeal bloodstream in order to reduce the risk of microemboli.

Referring to FIG. 1, a diagram 100 illustrates an extracorporeal bloodtreatment system for nitrogen gas removal from extracorporeal blood viachemical entrapment, according to one embodiment. As described furtherherein, the extracorporeal blood treatment system of FIG. 1 may enableefficient and continuous removal of microbubbles from an extracorporealbloodstream in order to reduce the risk of microemboli.

FIG. 1 illustrates an example of a medical treatment in which the bloodof a patient 102 is circulated outside of the patient's body fortreatment using an extracorporeal blood treatment unit 104. For ease ofillustration purposes, FIG. 1 depicts the extracorporeal blood treatmentunit 104 as a single unit. However, it will be appreciated thatalternative numbers and/or types of extracorporeal bloodstreamcirculation equipment may be utilized depending on the particularmedical treatment. As an illustrative, non-limiting example, for acardiopulmonary bypass procedure, the patient 102 may requireextracorporeal bloodstream treatment during the procedure, after theprocedure, or both. One challenge associated with such an extracorporealbloodstream treatment is that micro-leaks in the bloodstream circulationequipment and/or degassing effects from the blood may cause air bubblesto build up in the extracorporeal bloodstream. Re-insertion of such airbubbles into the patient 102 can lead to fatal embolisms. Accordingly,it is important to reduce or eliminate air bubbles from the treatedblood prior to re-insertion of the blood into the patient 102 in orderto reduce the risk of neurological impairment to the patient 102. FIG. 1illustrates that a drip chamber 106 (coupled to blood circulation tubing108) may enable partial mitigation of the air bubble removal problem. Aspreviously described herein, the drip chamber 106 may enable removal oflarger air bubbles, but removal of microbubbles remains a challenge.

FIG. 1 illustrates an example of an extracorporeal blood treatmentsystem in which an alumina particle 110 having an organometallic complex112 (e.g., a titanium complex) bound to a surface of the aluminaparticle 110 (identified as “Surface-Modified Alumina Particles” 114 inFIG. 1) may enable removal of microbubbles from extracorporeal blood viachemical entrapment of nitrogen (N₂) gas by dinitrogen fixation. Asnitrogen gas represents the majority of the air bubble content,complexation of nitrogen using the surface-modified alumina particles114 may result in collapse of the air bubbles (including microbubbles),thereby preventing the re-introduction of such air bubbles into thepatient 102.

In other embodiments, other types of particles may be utilized, such assilica or magnesia, among other alternatives. Further, variousorganometallic complexes have been demonstrated to sequester atmosphericnitrogen. Of the several organometallic complexes known to binddinitrogen, titanium complexes supported on alumina have beendemonstrated to result in the most effective dinitrogen fixation yield.Accordingly, while the present disclosure describes an example of atitanium complex bound to an alumina particle, it will be appreciatedthat alternative and/or additional types of particles and organometalliccomplexes may be utilized for microbubble removal from an extracorporealbloodstream.

While FIG. 1 illustrates an example of an extracorporeal blood treatmentsystem that includes an air bubble removal component (incorporatedwithin or downstream of the drip chamber 106) that has a single set ofsurface-modified alumina particles 114 (e.g., high surface areananoparticles having a particle size in a range of about 100 nm to 200nm), it will be appreciated that multiple types and/or arrangements ofparticles may be utilized for microbubble removal. For example, asillustrated and further described herein with respect to FIG. 2, theextracorporeal blood treatment system of the present disclosure mayinclude an air bubble removal component that utilizes multiple sets ofsurface-modified particles in different size ranges (with correspondingdifferences in surface area available for dinitrogen fixation). FIG. 2depicts one example of such an approach in which multiple particle“chambers” are arranged in series (with respect to the direction ofblood flow within the blood circulation tubing 108), with each chamberassociated with a different “stage” in a multiple-stage process ofchemical entrapment of nitrogen. Such a multiple-stage approach mayimprove the efficiency of nitrogen gas removal via chemical entrapment.It will be appreciated that the multiple-stage approach depicted in FIG.2 is an illustrative, non-limiting example and that alternative numbersand/or arrangements of chambers, particles, etc. may be used in order toimprove nitrogen fixation efficiency.

The surface-modified alumina particles 114 may be incorporated intovarious types of manufactured articles. For example, thesurface-modified alumina particles 114 may correspond to a powder thatis packed into a base of the drip chamber 106 where the extracorporealblood is permitted to flow after treatment by the extracorporeal bloodtreatment unit 104. Alternatively, while not shown in the example ofFIG. 1, the surface-modified alumina particles 114 may be incorporatedinto a separate microbubble removal chamber that may be downstream ofthe drip chamber 106 prior to re-introduction of the treated blood intothe patient 102.

In some cases, the surface-modified alumina particles 114 may beincorporated into the drip chamber 106 during manufacturing of the dripchamber 106. In other cases, the drip chamber 106 may correspond to aconventional drip chamber, and the surface-modified alumina particles114 may be incorporated into a separate article of manufacture that maybe connected to the drip chamber 106 or otherwise positioned downstreamof the drip chamber 106 in the extracorporeal blood stream. Thus, insome cases, a manufacturer of the drip chamber 106 may incorporate thesurface-modified alumina particles 114 into the drip chamber 106. Inother cases, the surface-modified alumina particles 114 may be disposedwithin a housing (such as the housing 202 depicted in FIG. 2) that mayinclude one or more coupling components to enable the housing to bepositioned downstream of the drip chamber 106. To illustrate, thehousing may include a male/female coupling component for attachment ofthe housing to a corresponding male/female coupling component of thedrip chamber 106. The housing may also include another couplingcomponent for insertion of the blood circulation tubing 108. It will beappreciated that the surface-modified alumina particles 114 may beincorporated into various alternative and/or additional manufacturedarticles to enable microbubble removal from an extracorporealbloodstream prior to re-insertion into the patient 102.

In a particular embodiment, the surface-modified alumina particles 114of FIG. 1 may include nanoparticulate alumina, such as a powder having ahigh surface area (e.g., in a range between 60 m²/g and 70 m²/g).Corundum (α-Al₂O₃) has significant importance in the field of catalyticapplications because it exists in a thermodynamically stable phase atstandard pressure and temperature conditions. However, its very lowsurface area represents a serious drawback. The “Pechini” method belongsto the sol-gel category of fabrication methods. In this method, anα-hydroxycarboxylic-containing compound forms a polybasic acid chelatewith metal cations which successively polymerize with a polyhydroxyalcohol. After a calcination process, nanometer-sized powders may beachieved. Compared to other sol-gel methods, the Pechini method hasbetter compositional homogeneity, lower toxicity and lower cost. In aparticular embodiment of the present disclosure, a modified water-basedPechini method may be utilized to prepare α-alumina nanoparticles thatare highly crystalline and have a high specific surface area (e.g., aBrunauer-Emmett-Teller (BET) surface area from 18 m²/g to 66 m²/g, ormore) at a relatively low calcination temperature of about 900° C. Toillustrate, alumina powders with a high specific surface area may beprepared using a polymerizing-chelating synthesis process. An example ofsuch a polymerizing-chelating synthesis process includes a polymerpreparation stage, followed by an alumina preparation stage.

As an illustrative, non-limiting example, the polymer preparation stagemay include mixing 0.12 mole of anhydrous citric acid with 0.1 mole ofanhydrous acrylic acid in the presence of 0.1% hydroquinone. The blendtemperature may be increased gradually to 120-170° C. Esterification mayoccur at about 120° C., and the polymerization may be carried out athigher temperatures to obtain a high viscosity polymer with awhite-yellowish color. The alumina preparation stage may include heating10 g of the previously prepared viscous polymer to 80° C. with stirring.The polymerizing-chelating, drying, and successive pyrolysis processesmay be performed using techniques known to one of ordinary skill in theart.

For example, the required volume of an aluminum nitrate nonahydratesolution with a desired concentration may be added to the polyester, andstirring may continue for about another hour. The solutions may then beslowly heated to 140° C. and maintained at this temperature untilremoval of water is nearly complete (about 2.5 hours). The resultingclear gel may be transferred to an electrical furnace and dried at 150°C. overnight, yielding a solid resin of high porosity. The resultingresin may be ground in an agate mortar and subjected to a pyrolysisprocess at 450° C. (heating rate 5° C./minute) for 4 hours in glazedalumina crucibles. Subsequently, the pyrolysis product may be subjectedto a calcination process at 900° C. (heating rate 5° C./minute) in thepresence of purified air.

In a particular embodiment, the organometallic complex 112 may include atitanium complex to sequester nitrogen gas from an air microbubble via acomplexation reaction that binds dinitrogen to the surface of thealumina particle 110. In a particular embodiment, the supported complexmay be prepared by reaction of a trichloro-cyclopentadienyl titaniumcompound (CpTiCl₃) with the surface hydroxyl groups of the aluminaparticle 110. The bound titanium (IV) complex is formally electrondeficient, rendering it susceptible to attack by the lone electron pairof dinitrogen.

As an illustrative, non-limiting example, the surface-modified aluminaparticles 114 depicted in FIG. 1 may be formed in two steps. In thefirst step, CpTiCl₃ may react with surface hydroxyl groups, leading toformation of Ti(IV) surface-bonded complexes and HCl (as depicted in thechemical reaction diagram shown in step 304 of FIG. 3). In the secondstep, the Ti(IV) surface complexes may be reduced with a reducing agent.An illustrative, non-limiting example of a reducing agent includes analkali metal naphthalene. To illustrate, reduction may include the useof sodium naphthalene (NaNp) or lithium naphthalene (LiNp) in a nitrogenatmosphere. In a particular embodiment, the bound titanium complex mayfirst be reduced with NaNp in a ratio exceeding 10:1, which may resultin a first dinitrogen fixation yield. When the titanium surface complexis first reduced with NaNp (e.g., at room temperature for 2 hours),washed, and dried, the dinitrogen fixation yield may increase to asecond dinitrogen fixation yield that is greater than the firstdinitrogen fixation yield.

Thus, FIG. 1 illustrates an example of an extracorporeal blood treatmentsystem for nitrogen gas removal from extracorporeal blood via chemicalentrapment. The extracorporeal blood treatment system of FIG. 1 mayenable efficient and continuous removal of microbubbles from anextracorporeal bloodstream in order to reduce the risk of microemboli.

FIG. 2 is a diagram 200 that illustrates selected portions of theextracorporeal blood treatment system depicted in FIG. 1 and thatillustrates a multiple-stage approach to chemical entrapment of nitrogengas using multiple particulate chambers, according to one embodiment.

In the multiple-stage approach depicted in FIG. 2, the air removalcomponent of the extracorporeal blood treatment system includes multiplenitrogen gas entrapment chambers disposed within a housing 202. FIG. 2illustrates that at least a first nitrogen gas entrapment chamber 204(identified as “N₂ Gas Entrapment Chamber(1)” in FIG. 2) and a secondnitrogen gas entrapment chamber 206 (identified as “N₂ Gas EntrapmentChamber(2)” in FIG. 2) are disposed within the housing 202. FIG. 2further illustrates that, in some cases, more than two nitrogen gasentrapment chambers may be disposed within the housing 202, with the(optional) additional nitrogen gas entrapment chamber(s) 208 representedby the integer n. In a particular embodiment, the additional nitrogengas entrapment chamber(s) 208 may correspond to a single additionalnitrogen gas entrapment chamber (i.e., n=3), representing a three-stageapproach to chemical entrapment of nitrogen gas.

FIG. 2 illustrates that the first nitrogen gas entrapment chamber 204may contain a first set of surface-modified alumina particles 210 (withone of the particles identified as “Surface-Modified AluminaParticle(1)” in FIG. 2). The second nitrogen gas entrapment chamber 206may contain a second set of surface-modified alumina particles 212 (withone of the particles identified as “Surface-Modified AluminaParticle(2)” in FIG. 2). In the particular embodiment depicted in FIG.2, where the multiple-stage approach includes at least three nitrogengas entrapment chambers, the at least one additional nitrogen gasentrapment chamber 208 includes a third set of surface-modified aluminaparticles 214 (with one of the particles identified as “Surface-ModifiedAlumina Particle(3)” in FIG. 2).

FIG. 2 illustrates that the different sets of particles disposed withinthe nitrogen gas entrapment chambers 204-208 may have different particlesize ranges and/or surface areas. For example, the first set ofsurface-modified alumina particles 210 may include alumina nanoparticleshaving an average particle size in a first particle size range, thesecond set of surface-modified alumina particles 212 may include aluminananoparticles having an average particle size in a second particle sizerange, and the third set of surface-modified alumina particles 214 mayinclude alumina nanoparticles having an average particle size in a thirdparticle size range.

In the particular embodiment depicted in FIG. 2, the air bubble removalcomponent of the extracorporeal blood treatment system corresponds to anarticle of manufacture that includes at least the housing 202, and thehousing 202 is separate from the drip chamber 106. In alternativeembodiments, the chemical entrapment components depicted within thehousing 202 may be “packed” into or otherwise disposed within a base ofthe drip chamber 106. FIG. 2 illustrates that, in cases where thehousing 202 is a separate article of manufacture from the drip chamber106, the housing 202 may include a first coupling component 220(identified as “Coupling Component(1)” in FIG. 2) to enable attachmentof the housing 202 to the drip chamber 106. FIG. 2 illustrates that thehousing 202 may further include a second coupling component 222(identified as “Coupling Component(2)” in FIG. 2) to enable insertion ofthe blood circulation tubing 108.

FIG. 2 depicts an illustrative, non-limiting example in which the firstset of surface-modified alumina particles 210 disposed within the firstnitrogen gas entrapment chamber 204 corresponds to the first stage ofchemical entrapment of nitrogen gas in air bubbles that may flow intothe housing 202 from the drip chamber 106. Accordingly, the first set ofsurface-modified alumina particles 210 encounters the highestconcentration of nitrogen gas in the bubbles (e.g., about 78 percent).As a result of nitrogen fixation in the first nitrogen gas entrapmentchamber 204, the second set of surface-modified alumina particles 212 inthe second nitrogen gas entrapment chamber 206 encounters a lowerconcentration of nitrogen gas in the bubbles (in cases where all bubbleshave not collapsed during the first stage). Nitrogen fixation in thesecond nitrogen gas entrapment chamber 206 further reduces theconcentration of nitrogen gas. In the example of FIG. 2, where there isat least one additional nitrogen gas entrapment chamber 208, the thirdset of surface-modified alumina particles 214 in the additional nitrogengas entrapment chamber(s) 208 encounters a still lower concentration ofnitrogen gas in any remaining bubbles that have not collapsed during thesecond stage.

As such, for improved nitrogen fixation efficiency, it may be desirableto utilize relatively small nanoparticles (also referred to herein as“high surface area” particles) as the first set of surface-modifiedalumina particles 210 in the first nitrogen gas entrapment chamber 204for the first stage of the multiple-stage chemical entrapment ofnitrogen gas. As a result of the reduction in the nitrogen gasconcentration in bubbles that have not collapsed prior to exiting thefirst nitrogen gas entrapment chamber 204, it may be possible to utilizelarger nanoparticles (also referred to herein as “medium surface area”particles) as the second set of surface-modified alumina particles 212.As a result of the further reduction in the nitrogen gas concentrationin bubbles that have not collapsed prior to exiting the second nitrogengas entrapment chamber 206, it may be possible to utilize still largernanoparticles (also referred to herein as “low surface area” particles)in the subsequent nitrogen gas entrapment chamber(s) 208. It will beappreciated that numerous other alternative sequences and/orarrangements may also be utilized. One example of an alternativethree-stage approach may include utilizing relatively high surface areaparticles, followed by relatively low surface area particles, followedby relatively high surface area particles.

Thus, in some embodiments, the first set of surface-modified aluminaparticles 210 may have a first average particle size, and the second setof surface-modified alumina particles 212 may have a second averageparticle size that is greater than the first average particle size.Further, in cases where more than two nitrogen gas entrapment chambersare utilized, the third set of surface-modified alumina particles 214may have a third average particle size that is greater than the secondaverage particle size. As illustrative, non-limiting examples, the firstaverage particle size may be in a range of 100 nm to 200 nm, the secondaverage particle size may be in a range of 400 nm to 500 nm, and thethird average particle size may be in a range of 800 nm to 1000 nm. Oneof ordinary skill in the art will appreciate that various particle sizeranges or combinations of particle size ranges that are sufficient tocause microbubble collapse due to chemical entrapment of nitrogen may beempirically determined.

Referring to FIG. 3, a flow diagram illustrates an example of a process300 of removing air bubbles from extracorporeal blood via chemicalentrapment of nitrogen gas, according to one embodiment. In theparticular embodiment illustrated in FIG. 3, the process 300 includesforming an alumina-supported organometallic complex and utilizing thealumina-supported organometallic complex to remove air bubbles fromextracorporeal blood via chemical entrapment of nitrogen gas. It will beappreciated that the operations shown in FIG. 3 are for illustrativepurposes only and that the operations may be performed in alternativeorders, at alternative times, by a single entity or by multipleentities, or a combination thereof. As an example, one entity may formalumina nanoparticles having an average particle size in desiredparticle size range(s), while another entity may form thealumina-supported organometallic complex (including reduction of thebound titanium complex for increased dinitrogen fixation yield), andanother entity may form an article of manufacture that includes thealumina-supported organometallic complex (e.g., a modified drip chamberor a component of a drip chamber). Further, yet another entity mayutilize the article of manufacture that includes the alumina-supportedorganometallic complex for removal of air bubbles (e.g., microbubbles)from extracorporeal blood via nitrogen sequestration.

The process 300 includes forming nanoparticulate alumina, at 302. Forexample, a modified water-based Pechini method may be utilized toprepare α-alumina nanoparticles that are highly crystalline and have ahigh specific surface area (as previously described herein with respectto FIG. 1). As an example, referring to FIG. 1, forming thenanoparticulate alumina may include forming the surface-modified aluminaparticles 114. As another example, in the case of a multiple-stageapproach such as the approach described with respect to FIG. 2, formingthe nanoparticulate alumina may include forming a first set of aluminananoparticles of a first size (e.g., the first set of surface-modifiedalumina particles 210 depicted in the first nitrogen gas entrapmentchamber 204) and forming a second set of alumina nanoparticles of asecond size (e.g., the second set of surface-modified alumina particles212 depicted in the second nitrogen gas entrapment chamber 206). In amultiple-stage approach that includes at least one additional nitrogengas entrapment chamber (e.g., the third nitrogen gas entrapment chamber208 of FIG. 2), the process 300 may further include forming one or moreadditional sets of alumina nanoparticles (e.g., the third set ofsurface-modified alumina particles 214 depicted in the third nitrogengas entrapment chamber 208 of FIG. 2).

The process 300 includes preparing an alumina-supported organometalliccomplex by treating the nanoparticulate alumina, at 304. For example,the organometallic complex may include a titanium (IV) complex. In thiscase, the nanoparticulate alumina may be treated with atrichloro-cyclopentadienyl titanium complex (CpTiCl₃), as previouslydescribed herein with respect to FIG. 1.

The process 300 also includes reducing the bound organometallic complexwith a reducing agent to increase dinitrogen fixation yield, at 306. Toillustrate, in the case of a titanium complex, the surface titaniumcomplex may be reduced with an alkali metal naphthalene (e.g., NaNp,LiNp, etc.) in a nitrogen atmosphere, as previously described hereinwith respect to FIG. 1.

The process 300 further includes utilizing the alumina-supportedorganometallic complex to remove air bubbles from extracorporeal bloodvia chemical entrapment of nitrogen gas by dinitrogen fixation, at 308.For example, the surface-modified alumina particles 114 depicted in FIG.1 may be utilized for microbubble removal via chemical entrapment of N₂gas. As another example, in a multiple-stage approach such as theapproach depicted in FIG. 2, multiple sets of surface-modified aluminaparticles may be utilized. For example, referring to FIG. 2, the firstset of surface-modified alumina particles 210 disposed within the firstnitrogen gas entrapment chamber 204 may be utilized for a first stage ofmicrobubble removal via chemical entrapment of N₂ gas, the second set ofsurface-modified alumina particles 212 may be utilized for a secondstage of microbubble removal, and the third set of surface-modifiedalumina particles 214 may be utilized for a third stage of microbubbleremoval.

Thus, FIG. 3 illustrates an example of a process of removing air bubblesfrom extracorporeal blood via chemical entrapment of nitrogen gas usingan organometallic complex bound to a surface of an alumina particle. Asdescribed further herein, the organometallic complex may be bound tonanoparticulate alumina that is treated to increase the number ofreactive sites on the surface of the alumina, thereby increasing theability of the active complex to bind dinitrogen. In some cases, thealumina-supported organometallic complex, in the form of a powder, maybe packed into the base of a drip chamber into which the extracorporealblood is permitted to flow (as depicted in the embodiment of FIG. 1). Asan alternative to a modified drip chamber, a separate microbubbleremoval chamber that includes the alumina-supported organometalliccomplex may be utilized. The high surface area and number of activenitrogen fixation sites of the nanoparticulate alumina powder may reducethe time required to sequester dinitrogen from the air microbubbles.Once nitrogen has been bound to the particle, the microbubble maycollapse, thereby reducing the risk of microemboli. Further, as depictedin the embodiment of FIG. 2, different sets of surface-modified aluminaparticles may be disposed within multiple nitrogen gas entrapmentchambers in a multiple-stage approach to chemical entrapment of nitrogengas.

It will be understood from the foregoing description that modificationsand changes may be made in various embodiments of the present inventionwithout departing from its true spirit. The descriptions in thisspecification are for purposes of illustration only and are not to beconstrued in a limiting sense. The scope of the present invention islimited only by the language of the following claims.

What is claimed is:
 1. An extracorporeal blood treatment systemcomprising: an air bubble removal component to remove air bubbles fromextracorporeal blood via chemical entrapment of nitrogen (N2) gas,wherein the air bubble removal component includes an organometalliccomplex to chemically entrap the nitrogen gas by dinitrogen fixation. 2.The extracorporeal blood treatment system of claim 1, wherein theorganometallic complex includes a titanium (IV) complex.
 3. Theextracorporeal blood treatment system of claim 1, wherein theorganometallic complex is bound to a surface of an alumina particle. 4.The extracorporeal blood treatment system of claim 3, wherein thealumina particle includes nanoparticulate alumina.
 5. The extracorporealblood treatment system of claim 4, wherein the nanoparticulate aluminaincludes a powder having a surface area in a range between 60 m2/g and70 m2/g.
 6. The extracorporeal blood treatment system of claim 1,wherein the air bubble removal component is disposed within a dripchamber.
 7. The extracorporeal blood treatment system of claim 1,wherein the air bubble removal component includes a housing having afirst nitrogen gas entrapment chamber packed with a first set ofsurface-modified alumina nanoparticles having a first average particlesize, the housing being disposed downstream of a drip chamber.
 8. Theextracorporeal blood treatment system of claim 7, wherein the housingfurther includes a second nitrogen gas entrapment chamber packed with asecond set of surface-modified alumina nanoparticles having a secondaverage particle size, the second nitrogen gas entrapment chamberdisposed downstream of the first nitrogen gas entrapment chamber.
 9. Theextracorporeal blood treatment system of claim 8, wherein the secondaverage particle size is greater than the first average particle size.10. The extracorporeal blood treatment system of claim 7, wherein thehousing includes a coupling component to enable attachment of thehousing to the drip chamber.
 11. The extracorporeal blood treatmentsystem of claim 1, further comprising a coupling component to enableinsertion of blood circulation tubing.
 12. The extracorporeal bloodtreatment system of claim 11, further comprising an extracorporeal bloodtreatment unit, wherein the blood circulation tubing is disposed betweenthe extracorporeal blood treatment unit and the air bubble removalcomponent.
 13. The extracorporeal blood treatment system of claim 12,wherein the air bubble removal component is downstream of theextracorporeal blood treatment unit.
 14. The extracorporeal bloodtreatment system of claim 13, further comprising a drip chamber, whereinthe drip chamber is disposed between the extracorporeal blood treatmentunit and air bubble removal component.
 15. The extracorporeal bloodtreatment system of claim 13, further comprising a drip chamber, whereinthe air bubble removal component is disposed within the drip chamber.16. An extracorporeal blood treatment system comprising: anextracorporeal blood treatment unit; a drip chamber; and an air bubbleremoval component to remove air bubbles from extracorporeal blood viachemical entrapment of nitrogen (N₂) gas, the chemical entrapmentcomprising dinitrogen fixation by an organometallic complex.